Conventional prostate cancer therapies sometimes fail to provide satisfactory treatment results, while the side effects often significantly degrade patient quality of life. A more localized cancer treatment modality with minimal side effects is desired for the management of prostate cancer. Photodynamic therapy (PDT) utilizes locally delivered light energy to activate a pre-administered photosensitizer, which ultimately leads to controlled destruction of target tissue. Our objective, thus, is to develop PDT as an alternative/adjunctive therapy for prostate cancer by total prostate ablation. The specific aims are: (1) to optimize the PDT treatment schedules in prostate employing both the Dunning tumor model in rat and both normal and pre-irradiated canine prostate, (2) to determine the PDT damage threshold produced by varying photosensitizer and light doses, (3) to develop a treatment planning and monitoring technique using multi-purpose optical probes for accurate prostate ablation, and (4) to validate the procedures in an in vivo model for total prostate ablation. For the above investigations we propose to employ a unique second generation photosensitizer, Tookad, which acts primarily on local vasculature, and requires literally no waiting period between administration and light irradiation. This sensitizer has a rapid clearance from the body and is essentially cleared completely from all critical tissues within one day. We will qualitatively evaluate the photosensitizer pharmacokinetics. Optical probes will be used to measure dynamic light fluence distribution and tissue oxygenation during PDT. PDT induced lesions will be evaluated histopathologically and correlated to the treatment dosimetry for a damage threshold value. Similar procedures will be performed for adjacent structures. Based on the threshold values and information collected from the studies, we will develop treatment planning and monitoring techniques for our ultimate goal: total prostate ablation with minimal damage to adjacent structures. The procedures then will be tested in canine prostates pre-treated with ionizing radiation to simulate the conditions in patients who have failed conventional radiation therapy. The completion of the project will, thus, provide physicians with directly applicable information and techniques to plan clinical trials of PDT on human patients with prostate cancer.